The American Medical Association classified obesity as a disease in 2013 (Morgen & Sorenson, 2014), and as a leading preventable cause of death worldwide a clearer understanding of its genetic and molecular underpinnings has never been more important (Morgen & Sorenson, 2014; Malik, et al., 2013). Obesity is caused by an imbalance between energy intake and output (Spiegelman, et al., 2001; Spiegelman, et al., 1996). Because of the number of organs that impact these two processes and the complexity of energy homeostasis, the study of obesity remains a significant scientific challenge (Spiegelman, et al., 2001). Historically, study of extreme human variation has been a powerful tool for solving complex biological problems and for developing therapeutic targets against disease (Goldstein, et al., 2009; Friedman, et al., 2009). The present disclosure describes the loss of a new circulating polypeptide hormone responsible for maintenance of fat mass and associated glycemic control as the molecular mechanism driving the phenotype of an extreme thinness disorder in humans known as Neonatal Progeroid Syndrome (NPS) (Hou, et al., 2009; O'Neill, et al., 2007).